Conjugate formation between cytotoxic T lymphocytes (CTL) and target cells (TC) results in dramatic consequences for both. TC will be destroyed and CTLs receive a biochemical signal for activation and start to proliferate and to release lymphokines. Several proteins on the surface of CTL were implicated in such interactions (e.g., LFA-1, T200, Lyt2.2, T cell receptor-T3 complex), but it is not known how they are organized on the surface of CTL, although we have circumstantial evidences that T cell receptor-T3 molecules are part of a bigger multimolecular complex. In the studies started at the NIH, we are trying to evaluate distribution of different molecules in the lymphocyte plasma membrane and to demonstrate multimolecular complexes on the surface of CTL using whole cloned cells, purified preparations of plasma membranes, monoclonal antibodies, and heterobifunctional crosslinking reagents. Preliminary results suggest that there is an asymmetrical distribution of surface proteins between different domains of lymphocyte plasma membranes.